Side-by-side analysis of five clinically tested anti-EpCAM monoclonal antibodies.

Background: Epithelial cell adhesion molecule (EpCAM) is frequently and highly expressed on human carcinomas. The emerging role of EpCAM as a signalling receptor and activator of the wnt pathway, and its expression on tumor-initiating cells, further add to its attractiveness as target for immunotherapy of cancer. Thus far, five conventional monoclonal IgG antibodies have been tested in cancer patients.

Model-based prediction of phase III overall survival in colorectal cancer on the basis of phase II tumor dynamics.

Purpose: We developed a drug-disease simulation model to predict antitumor response and overall survival in phase III studies from longitudinal tumor size data in phase II trials.

Methods: We developed a longitudinal exposure-response tumor-growth inhibition (TGI) model of drug effect (and resistance) using phase II data of capecitabine (n = 34) and historical phase III data of fluorouracil (FU; n = 252) in colorectal cancer (CRC); and we developed a parametric survival model that related change in tumor size and patient characteristics to survival time using historical phase III data (n = 245). The models were validated in simulation of antitumor response and survival in an independent phase III study (n = 1,000 replicates) of capecitabine versus FU in CRC.

Response to chemoradiatiotherapy in squamous cell carcinoma of the esophagus: evaluation of some prognostic factors.

Objective: To evaluate the predictive values of the expression of factor VIII, CD-34, p53, bcl-2, and DNA ploidy regarding the response to chemoradiation of squamous cell carcinoma of the esophagus.

Design: Retrospective analysis of pretreatment biopsies with immunohistochemistry and flow cytometry. The results were correlated to tumor response (complete vs.

Esophageal cancer in Stockholm county 1978-1995.

Background: Most studies regarding esophageal cancer are based on a selection of patients, influencing the prognosis as well as other variables measured. Sweden may be unique in that it has registries that cover the whole population, permitting population based studies regarding diseases such as esophageal cancer. This also makes it possible to study the true nature of a population of patients and to describe changes in that population over time.

Capecitabine as adjuvant treatment for stage III colon cancer.

Background: Intravenous bolus fluorouracil plus leucovorin is the standard adjuvant treatment for colon cancer. The oral fluoropyrimidine capecitabine is an established alternative to bolus fluorouracil plus leucovorin as first-line treatment for metastatic colorectal cancer. We evaluated capecitabine in the adjuvant setting.

Clinical effects of a chimeric anti-EpCAM monoclonal antibody in combination with granulocyte-macrophage colony-stimulating factor in patients with metastatic colorectal carcinoma.

The EpCAM antigen is highly expressed on colorectal carcinoma (CRC) cells. Murine anti-EpCAM MAb (anti-EpCAM mMAb) alone or in combination with cytokines may induce clinical responses including long-lasting complete remissions (CR) in patients with metastatic disease. The chimeric variant of anti-EpCAM MAb (anti-EpCAM cMAb) interacts more efficiently with human effector cells (ADCC) than the murine counterpart in the killing of colorectal carcinoma cells in vitro, an important mechanism of action for antibody in vivo.

T-cell receptor BV gene usage in colorectal carcinoma patients immunised with recombinant Ep-CAM protein or anti-idiotypic antibody.

The tumour-associated antigen, Ep-CAM, is over-expressed in colorectal carcinoma (CRC). In the present study, a recombinant Ep-CAM protein or a human anti-idiotypic antibody (anti-Id) mimicking Ep-CAM, either alone or in combination, was used for vaccination of CRC patients (n=9). GM-CSF was given as an adjuvant cytokine.

Targeting human Ep-CAM in transgenic mice by anti-idiotype and antigen based vaccines.

Anti-idiotypic antibodies (anti-Id) as surrogate TAAs have been shown to induce immunity against tumours in animals and humans. SM262 is a human monoclonal anti-Id raised against MAb 17-1A recognising Ep-CAM. Plasmids encoding the variable regions of SM262 with either murine or human Fc regions, both with and without fusion to GM-CSF were constructed.

Vaccination with Ep-CAM protein or anti-idiotypic antibody induces Th1-biased response against MHC class I- and II-restricted Ep-CAM epitopes in colorectal carcinoma patients.

Purpose: The tumor-associated antigen Ep-CAM (epithelial cell adhesion molecule) is overexpressed in colorectal carcinoma (CRC). The aim of the present study was to evaluate and compare the safety and immunogenicity of a recombinant Ep-CAM protein and a human anti-idiotypic antibody (anti-Id) mimicking Ep-CAM.

Experimental Design: Patients with resected American Joint Committee on Cancer stages II-IV CRC without remaining macroscopic disease received intradermal/subcutaneous injections of Ep-CAM (400 microg/dose; n = 7) or anti-Id (500 microg/dose; n = 6) at weeks 0, 2, and 6 in combination with granulocyte macrophage colony-stimulating factor (75 microg/day, for 4 consecutive days).

Functional HLA-DR T cell epitopes of CEA identified in patients with colorectal carcinoma immunized with the recombinant protein CEA.

A baculovirus-produced recombinant CEA (rCEA) protein comprising the extracellular region was used for vaccination of CRC patients with or without GM-CSF as an adjuvant cytokine. Ten patients with a significant proliferative T cell response against rCEA were selected for T cell epitope mapping. Fifteen-aa-long overlapping peptides covering the entire aa sequence of the external domain of CEA were used in a proliferation assay.

T-cell epitopes within the complementarity-determining and framework regions of the tumor-derived immunoglobulin heavy chain in multiple myeloma.

The idiotypic structure of the monoclonal immunoglobulin (Ig) in multiple myeloma (MM) might be regarded as a tumor-specific antigen. The present study was designed to identify T-cell epitopes of the variable region of the Ig heavy chain (VH) in MM (n = 5) using bioinformatics and analyze the presence of naturally occurring T cells against idiotype-derived peptides. A large number of human-leukocyte-antigen (HLA)-binding (class I and II) peptides were identified.

Serial fine needle cytology in the diagnosis of esophageal cancer.

Objective: To describe a method of registering local spread of cancer in the esophageal wall through serial endoscopic fine needle aspiration (FNA), to evaluate FNA as a diagnostic tool as compared to histologic biopsies and brush cytology, and to investigate cytologic appearances of aspirates and correlate them with survival

Study Design: Fifty-two patients with esophageal cancer were investigated with serial FNA every second centimeter from the upper esophageal sphincter aborally down to the level of macroscopic tumor. Histologic biopsies and brush cytologies were then performed.

Results: Of investigated cases, 33% showed malignant or suspect malignant cells from macroscopic tumor, at > or = 4 cm orally, as did 3 of 12 patients at 14 cm.

MAb17-1A and cytokines for the treatment of patients with colorectal carcinoma.

CO17-1A/GA73-3/EpCam/KSA is a cellular adhesion molecule expressed on the majority of tumor cells in most patients with colorectal carcinoma. One of the first mouse monoclonal antibodies (MAbs) for therapeutic use was produced against this particular tumor associated antigen (MAb17-1A). MAb17-1A has served as a model for the development of antibody therapy.

Immunogenic regions of the GA733-2 tumour-associated antigen recognised by autoantibodies of patients with colorectal carcinoma.

The tumour-associated antigen (TAA) GA733-2 is overexpressed by >90% of human colorectal carcinomas (CRC). The antigen has previously been shown to be recognised by B and T cells. The aim of the present study was to define B cell epitopes of GA733-2.